Spinal Anesthesia in a Patient with Prekallikrein Deficiency

Spinal Anesthesia in a Patient with Prekallikrein Deficiency
Shital K. Pasricha, MD, Hallie Weiss, MD, and Amy Chen, MD
Department of Anesthesiology, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New York,
New York
P
rekallikrein deficiency, also known as Fletcher
factor deficiency prolongs the activated partial
thromboplastin time (aPTT) and whole blood
clotting time. In 1965 Hathaway et al. (1) reported four
siblings with Fletcher factor deficiency in a consanguineous
union. Since then other cases have been
documented. This rare, congenital defect is thought to
be an autosomal recessive disorder with incomplete
penetrance in females, with lower levels of prekallikrein
in males as compared to females (2). It produces
a prolongation of whole blood clotting time, a markedly
prolonged aPTT, slight lengthening of the thromboelastogram,
a normal prothrombin time, bleeding
time, and thrombin time. Patients with this disease
present without clinical evidence of coagulopathy despite
a prolonged aPTT on laboratory testing. We describe
the anesthetic management of a cesarean section
for a patient with prekallikrein deficiency.
Case Report
A 28-yr-old black female gravida 9 para 1 (G9P1071) was
admitted to the labor and delivery suite at 26 wk gestational
age with rupture of membranes. She had sickle cell trait with
hemoglobin S of 39.6% and was known to possess an anticardiolipin
antibody. She also had a history of increased
arterial blood pressure in a previous pregnancy in 1982 and
therefore had been given 60 mg aspirin per day during this
pregnancy. She had no history of gum or nose bleeds, easy
bruising, menorrhagia, excessive bleeding after surgery, or
deep vein thrombosis. She had never required a blood transfusion.
On admission, arterial blood pressure was 144/
81 mm Hg with a heart rate of 116 bpm. She weighed 124 kg
and was 175 cm tall. Results of her routine laboratory examinations
were within normal limits with the exception of an
aPTT of 108.5 s. The prothrombin time was 12.3 s and the
blood fibrinogen level was 506 mg. Additions of fresh frozen
plasma corrected her aPTT to 27.6 s at 0 h and 30.7 s at 2 h,
suggesting a factor deficiency rather than the presence of an
inhibitor. A search for a lupus anticoagulant revealed a
positive cardiolipin antibody with increased immunoglobulin
G of 26.4 (N O-23), and normal immunoglobulin M of 7.1
Accepted for publication August 15, 1996.
Address correspondence and reprint requests to Shital K.
Pasricha, MD, Department of Anesthesiology, Long Island Jewish
Hospital, New Hyde Park, NY 11040.
01996 by the International Anesthesia Research Society
0003-2999/96/$5.00
(N O-11). Platelet neutralization studies and dilute Russell
viper venom time (37.9 s) were normal, indicating that the
aPTT prolongation was not due to the lupus anticoagulant.
Further investigation revealed prekallikrein levels of 9.9%
(N 50%-150%).
Approximately 48 h after admission she went into labor
and was scheduled for cesarean section for transverse lie.
Spinal anesthesia was administered with a 24-gauge Sprotte
needle using bupivacaine 12 mg, fentanyl 15 pg, and du-
ramorph 0.3 mg. The patient did well and there were no
surgical or anesthetic complications.
Discussion
Prekallikrein is a protein with an approximate molec-
ular weight of 100,000 daltons. It participates in the
coagulation, fibrinolysis, and the plasma kinin-
generating systems. Prekallikrein deficiency is also
known as Fletcher factor deficiency because it was
first diagnosed in the Fletcher family in Kentucky in
1963.
Prekallikrein is required for the complete activation
and optimal functioning of factor XII. In prekallikrein
deficiency, the activation of factor XII and, therefore,
the intrinsic pathway of coagulation, proceeds slowly,
resulting in prolongation of the aPTT. By increasing
the contact time with activator from three to five min-
utes to 10 minutes during the PTT test, enough of
factor XII, is generated to correct the PTT in prekalli-
krein deficiency.
In the fibrinolytic system, plasminogen is activated
by several activators including kallikrein and factor
XII,.
Plasma kallikrein produces kinins from high molec-
ular weight kininogen, which are involved in various
inflammatory processes, uterine contractility during
labor and delivery (3), and various pathological states
such as shock, allergic conditions, burns, and arthritis.
In addition to congenital deficiency, acquired pre-
kallikrein deficiency has been reported in liver dis-
ease, septic shock, chronic renal failure, vitamin K
deficiency, multiple trauma, disseminated intravascu-
lar coagulation, typhoid fever, blood component ther-
apy, deep vein thrombosis, and phlebitis. Even though
affected people usually have a markedly prolonged
Anesth Analg 1996;83:1325-6 1325

1326 CASE REPORTS ANESTH ANALG
1996;83:1325-6
aPTT, they do not experience increased clinical bleed-
ing even when stressed by surgery, suggesting that
contact mechanisms of clotting have only a minor role
in normal in vim hemostatic function. Harris et al. (4)
suggested that anticoagulants may potentiate the risk
of major bleeding episodes in the affected patients.
Prekallikrein may not be important for normal in
vim fibrinolysis, which may operate via tissue or ves-
sel wall fibrinolytic activator release. However, in the
presence of an atheroma in a blood vessel, reduced
local vascular fibrinolysis may predispose these pa-
tients to increased arterial thrombosis. In 1976 Currim-
bhoy et al. (5) reported a case of myocardial infarction
in a patient with Fletcher factor deficiency and the
possibility of impaired fibrinolysis contributing to
thrombosis was postulated.
Severe prekallikrein deficiency in humans is not
associated with any clinically significant impairment
of hemostasis, fibrinolysis, or inflammatory response.
In most cases, prekallikrein deficiency is a laboratory
nuisance, especially in preoperative testing of surgical
patients. A prolonged aPTT triggers a hemostatic
alarm and necessitates the performance of several
complex and time-consuming tests to elucidate the
problem. Based upon our current understanding of
prekallikrein deficiency, the risk of developing central
neuraxial bleeding from the administration of spinal
anesthesia is not &creased in patients who demonstrate
this hereditary disorder.
References
1. Hathaway WE, Belhasen LP, Hathaway MS. Evidence for a new
plasma thrombo-plastin factor. Blood 1965;26:521-5.
2. Hattersley PG, Hayse D. Fletcher factor deficiency: a report of
three unrelated cases. Br J Haematol 1970;18:411-6.
3. Shigenori S, Wataru S. The kinetics of blood coagulability, fibrinolytic
and kallikrein-kinin system at the onset and during
labor. Eur J Obstet Gynecol Reprod Biol 1984;17:209-18.
4. Harris MG, Exner T, Rickard KA, et al. Multiple cerebral thrombosis
in Fletcher factor (prekallikrein) deficiency. , Am - J Hematol
1985;19:387-93. -
5. Currimbhoy Z, Vinciguerra V, Palakavongs P, et al. Fletcher
factor deficiency and myocardial infarction. Am J Clin Path01
1976;65:970-4.